Enhancing miRNAs Capture on Polydimethylsiloxane Surface with Nanostructuration

Abstract

IntroductionIn the last years, predictive and preventive medicine took advantage on the novel discoveries in nano-diagnostics and smart therapies, mainly based on the specific identification of molecular biomarkers, such as nucleic acids (DNA, miRNA) and proteins. The possibility to detect low amount of biomarkers directly in biological fluids gives a great advantage in the early diagnosis and therapy of malignant diseases, which have high social impact. In fact, a correlation between degenerative, contagious, or inflammatory illnesses with the presence of specific biomarkers like miRNAs is now well established [1][2][3][4][5]. However, this remains a challenging task since in each biological sample several different biomolecular species co-exist, and moreover it is very hard to treat them in order to achieve the degree of purity and concentration required for a quantitative, specific, and reliable identification. To overcome these obstacles, several nanotechnologybased systems are being developed and tested for miRNAs detection. Nanobiosensor development is particularly relevant for such miRNAs, whose aberrant expression has been shown to correlate with the pathogenesis and progression of several diseases including cancer [6,7]. , in particular, is largely studied since is overexpressed in a variety of solid [8,9] and hematological tumors [10,11]. For these reasons, miR-21 was selected as a microRNA prototype in this study.Recently, it has been proposed that nanotechnology-based approaches [12][13][14] alternative to conventional methods [15][16][17][18][19] for miRNA detection and quantification can be developed using innovative biosensors made of Polydimetylsiloxane (PDMS) [20][21][22]. PDMS is known to have numerous advantages, supporting its development as a useful platform for biosensor and biomedical applications [20,[23][24][25]. Particularly, the attractiveness of such polymer lies in the fact that its chemical and physical properties and also the surface topography can be modulated [26]. These features combined with the manufacturing of biomolecule-specific topographies contribute to the improvement of PDMS performance in terms of sensitivity and efficiency. Recently, the fabrication of PDMS-based devices has introduced significant advances in several analytical techniques in terms of sensitivity, time consuming, and sample volume. Since PDMS material revealed characteristic properties and reliability, PDMS-nanotechnology has therefore gained great attention in developing new generation of research tools. However, both traditional and technology-based approaches have yet limitations mainly related to sample processing, purification, separation and enrichment of the small RNA fraction [12,27]. In fact, advanced biosensors still require specific conjugation steps [28] and expensive equipment which need to be overcome before they can have a real clinical application.PDMS nanostructures manufacturing may be useful to enhance the efficient purification of miRNA circulating bio-markers present at low Abstrac...